Alteration of heat shock protein 20 expression in preeclamptic patients and its effect in vascular and coagulation function / 医学前沿

Preeclampsia (PE) is a pregnancy-specific, multi-system disorder and the leading cause of maternal and perinatal morbidity and mortality in obstetrics worldwide. Excessive vasoconstriction and dysregulated coagulation function are closely associated with PE. Heat shock protein 20 (HSP20) is ubiquitously expressed under normal physiological conditions and has important roles in vascular dilatation and suppression of platelet aggregation. However, the role of HSP20 in the pathogenesis of PE remains unclear. In this study, we collected chorionic plate resistance arteries (CPAs) and serum from 118 healthy pregnant women and 80 women with PE and detected the levels of HSP20 and its phosphorylated form. Both HSP20 and phosphorylated HSP20 were downregulated in CPAs from women with PE. Comparison of the vasodilative ability of CPAs from the two groups showed impaired relaxation responses to acetyl choline in preeclamptic vessels. In addition to the reduced HSP20 in serum from women with PE, the platelet distribution width and mean platelet volume were also decreased, and the activated partial thromboplastin time and thromboplastin time were elevated.With regard to the vital roles of HSP20 in mediating vasorelaxation and coagulation function, the decreased HSP20 might contribute to the pathogenesis of PE.

Research progress on vascular pharmacologic effects of oleanolic and ursolic acids / 药物评价研究

Ursolic and oleanolic acids antagonize ox-LDL-,C-reactive protein-,non-enzymatic glycation end products-,hyper-glucose-,H2O2-,lipopolysaccharide-induced endothelial cell injury,and their vascular pharmacologic effects are in many ways.Ursolic and oleanolic acids can inhibit the proliferation of vascular smooth muscle cells,and antagonize serum-,ox-LDL-,hyper-glucose-,leptin-induced vascular smooth muscle cell proliferation,thus produce vascular protection and improve vascular function;Ursolic and oleanolic acids can relieve diabetic vascular complication in diabetic mellitus rats,and vascular stenosis induced by carotid balloon catheter injury,and suppress the proliferation of vascular adventitial fibroblasts and prevent vascular stenosis induced by various experimental atherosclerosis models;they can also inhibit the proliferation of vascular endothelial cells,and have a dual action to antagonize inhibiting or promoting proliferation induced by various injurious factions.Thus they have a dual role of regulation in angiogenesis,and suppress angiogenesis of cornea,diabetic retina,and tumor tissues,have effects of vascular relaxation and resistance decrease,and have hypotensive effects in normal and various hypertensive animals.

The Labdane Ent-3-Acetoxy-Labda-8(17), 13-Dien-15-Oic Decreases Blood Pressure In Hypertensive Rats / O Labdano Ácido Ent-3-Acetóxi-Labda-8(17), 13-Dieno-15-Óico Reduz Pressão Arterial Em Ratos Hipertensos

Abstract Background: Labdane-type diterpenes induce lower blood pressure via relaxation of vascular smooth muscle; however, there are no studies describing the effects of labdanes in hypertensive rats. Objective: The present study was designed to investigate the cardiovascular actions of the labdane-type diterpene ent-3-acetoxy-labda-8(17), 13-dien-15-oic acid (labda-15-oic acid) in two-kidney 1 clip (2K-1C) renal hypertension. Methods: Vascular reactivity experiments were performed in aortic rings isolated from 2K-1C and normotensive (2K) male Wistar rats. Nitrate/nitrite (NOx) measurement was performed in aortas by colorimetric assay. Blood pressure measurements were performed in conscious rats. Results: Labda-15-oic acid (0.1-300 µmol/l) and forskolin (0.1 nmol/l - 1 µmol/l) relaxed endothelium-intact and endothelium-denuded aortas from both 2K-1C and 2K rats. Labda-15-oic acid was more effective at inducing relaxation in endothelium-intact aortas from 2K pre-contracted with phenylephrine when compared to the endothelium-denuded ones. Forskolin was more potent than labda-15-oic acid at inducing vascular relaxation in arteries from both 2K and 2K-1C rats. Labda-15-oic acid-induced increase in NOx levels was lower in arteries from 2K-1C rats when compared to 2K rats. Intravenous administration of labda-15-oic acid (0.3-3 mg/kg) or forskolin (0.1-1 mg/kg) induced hypotension in conscious 2K-1C and 2K rats. Conclusion: The present findings show that labda-15-oic acid induces vascular relaxation and hypotension in hypertensive rats.

Resumo Fundamento: Diterpenos do tipo labdano induzem uma queda da pressão arterial por meio do relaxamento do músculo liso vascular; todavia, não há estudos que descrevam os efeitos de labdanos em ratos hipertensos. Objetivo: O presente estudo foi desenvolvido para investigar as ações cardiovasculares do labdano ácido ent-3-acetóxi-labda-8(17),13-dieno-15-óico (labda-15-óico) na hipertensão renal dois rins-1 clipe (2R-1C). Métodos: Foram feitos experimentos de reatividade vascular em anéis aórticos isolados de ratos machos 2R-1C e normotensos (2R). A medição de Nitrato/Nitrito (NOx) foi feita nas aortas por meio de ensaio colorimétrico. As medidas de pressão arterial foram feitas em ratos conscientes. Resultados: O ácido labda-15-óico (0,1 - 300 µmol/l) e a forscolina (0,1 nmol/l - 1 µmol/l) relaxaram as aortas com endotélio intacto e as aortas sem endotélio dos ratos 2R-1C e 2R. O labda-15-óico mostrou-se mais eficaz na indução do relaxamento em aortas com endotélio intacto de 2R pré-contraídas com fenilefrina em comparação àquelas sem endotélio. A forscolina mostrou-se mais potente do que o ácido labda-15-óico na indução do relaxamento vascular nas artérias tanto de ratos 2R-1C quanto de ratos 2R. O aumento dos níveis de NOx induzido pelo ácido labda-15-óico foi menor nas artérias de ratos 2R-1C em comparação a ratos 2R. A administração intravenosa de ácido labda-15-óico (0,3-3 mg/kg) ou forscolina (0,1-1 mg/kg) induziu hipertensão em ratos 2R-1C e 2R conscientes. Conclusão: Os presentes resultados mostram que o labda-15-óico induz relaxamento vascular e hipotensão em ratos hipertensos.

Nafamostat mesilate promotes endothelium-dependent vasorelaxation via the Akt-eNOS dependent pathway

Nafamostat mesilate (NM), a synthetic serine protease inhibitor, has anticoagulant and anti-inflammatory properties. The intracellular mediator and external anti-inflammatory external signal in the vascular wall have been reported to protect endothelial cells, in part due to nitric oxide (NO) production. This study was designed to examine whether NM exhibit endothelium dependent vascular relaxation through Akt/endothelial nitric oxide synthase (eNOS) activation and generation of NO. NM enhanced Akt/eNOS phosphorylation and NO production in a dose- and time-dependent manner in human umbilical vein endothelial cells (HUVECs) and aorta tissues obtained from rats treated with various concentrations of NM. NM concomitantly decreased arginase activity, which could increase the available arginine substrate for NO production. Moreover, we investigated whether NM increased NO bioavailability and decreased aortic relaxation response to an eNOS inhibitor in the aorta. These results suggest that NM increases NO generation via the Akt/eNOS signaling pathway, leading to endothelium-dependent vascular relaxation. Therefore, the vasorelaxing action of NM may contribute to the regulation of cardiovascular function.

Influence of anisodamine on in vitro vascular relaxation function in normal and spontaneous hypertension rats / 第二军医大学学报

Objective: To observe the influence of anisodamine on relaxation function of isolated Wistar and spontaneously hypertensive rat (SHR) aortic rings, and to investigate the underlying mechanism. Methods: The SHR aorta rings were irrigated with anisodamine and the effect of anisodamine on relaxation of isolated aortic rings was observed in normal and spontaneous hypertension rats before and after pretreatment with phenylephrine (PE) or L-nitroarginine methylester (L-NAME). Results: The accumulated concentration of anisodamine showed significantly different relaxing effects on PE-precontracted aortic ring with or without endothelium (P0.05). Pretreatment with non selective NOS inhibitor L-NAME significantly inhibited the relaxing effect of anisodamine on the aortic ring with endothelium (P<0.05). L-NAME partially blocked the relaxing effect of anisodamine on SHR rats, with the maximal relaxation being 61% and 11.9% (P<0.01) before and after blocking, respectively. Conclusion: Anisodamine can enlarge isolated aorta of rats through endothelial and smooth muscle.

The experimental study of vascular relaxation induced by the ethanol extract of Blueberry(BE) / 中国基层医药

Objective To study the effects and the mechanism of the ethanol extract of Blueberry(BE) on relaxation vascular endothelium or smooth muscle.Methods To use rat aorta as the specimen,to observe the effects of BE on induced relaxation of the phenylephrine-precontracted aorta.and approach the mechanism on vascular endothelium or smooth muscle.Results BE induced relaxation of the phenylephrine-precontracted(1.0×10~(-5)mol·L~(-1) aorta in a dose-dependent way(P<0.01),which was disappeared by removal of functional endothelium(P<0.01).Pretreatment of the aortic tissues with NG-nitro-L-arginine methyl ester(L-NAME),methylene blue,or 1H[1,2,4]-oxadiazole-[4,3_a]-quinoxalin-1-one (ODQ) inhibited the vascular relaxation induced by BE(P<0.01).BE-induced vascular relaxations were also markedly attenuated by addition of verapamil or diltiazem,while the relaxant effect of BE was not blocked by pretreatment with indomethacine,glibenclamide,tetraethylammonium(TEA),atropine,propranolol(P<0.01).Conclusion These results suggest that BE dilates vascular smooth muscle via endothelium-dependent nitricoxide-cGMP signaling pathway,possible involvement of L-type Ca~(2+) channel.

Function alteration of aortas at different stages of type Ⅱ diabetes rats / 中国临床药理学与治疗学

AIM: To investigate the alteration of the vascular response to contracting material and the endothelium dependent vascular relaxation (EDVR) at different stages of type Ⅱ diabetes rats. METHODS: Type Ⅱ diabetes rat model was established by high-energy diet and lower dose of STZ. At 12th and 20th weekends after injecting STZ, the vascular reactivities to phenylephrine (PHE) and KCl and the EDVR induced by Ach were measured respectively in the isolated aorta rings. RESULTS: At 12th weekend after injecting STZ, the response to PHE increased, the reactivity to KCl kept unchanged, and the EDVR was damaged lightly. But at the 20 th weekend after injecting STZ, the response to PHE increased further and the reactivity to KCl markedly reinforced, and the EDVR was obviously damaged. CONCLUSION: The response of great vessels to contracting material increased, but the EDVR attenuated at different stages of type Ⅱ diabetes rats. These changes are further reinforced along with the developing of disease duration.

Comparison of Vasodilator Effects of Platycodin D and D3 in Rats

The aim of the present study was to examine the effects of platycodin D and D3, which are active components derived from the roots of Platycodon grandiflorum A. DC., on the contractile force of the i3olated rat aorta and blood pressure of the anesthetized rat, and also to elucidate its mechanism of action. Both phenylephrine (an adrenergic alpha1-receptor agonist) and high potassium (a membrane- depolarizing agent) caused great contractile responses in the isolated aortic strips. Platycodin D at high concentration (24microgram/ml) inhibited contractile responses induced by phenylephrine (10 (-5) M) and high potassium (5.6x10 (-2) M), while low concentrations of platycodin D (4~8microgram/ml) did not affect those responses. However, platycodin D3 (8~32microgram/ml) did not alter the contractile responses evoked by phenylephrine and high K+. Interestingly, the infusion of platycodin D3 (1.0 mg/kg/30 min) significantly reduced the pressor responses induced by intravenous norepinephrine. However, platycodin D3 (1.0 mg/kg/30 min) did not affect them. Taken together, these results show that intravenously administered platycodin D depresses norepinephrine-induced pressor responses in the anesthetized rat, at least partly through the blockade of adrenergic alpha1-receptors. Platycodin D also caused vascular relaxation in the isolated aortic strips of the rat via the blockade of adrenergic alpha1-receptors, in addition to an unknown direct mechanism. However, platycodin D3 did not affect both norepinephrine-induced pressor responses and the isolated rat aortic contractile responses evoked by phenylephrine and high potassium. Based on these results, there seems to be much difference in the mode of action between platycodin D and platycodin D3.

Effects of H_2O_2 and 11,12-EET in EDHF mediated relaxation in the rat basilar arteries / 中国临床药理学与治疗学

AIM:To study the effects of Hydrogen Peroxide(H2O2)and 11,12-epoxyeicosatrienoic acid(11,12-EET)on EDHF-mediated relaxation in the rat basilar arteries.METHODS: The relaxant effects of acetylcholine(ACh),H2O2,11,12-EET,and catalase(CAT) on rat arteria basilaris in vitro were detected by vasomotoricity experiment in vitro.RESULTS: In the rat basilar arteries,preconstricted by 30 mmol/L KCl in vitro,ACh(10-7-10-4.5 mol/L) had the concentration-dependent relaxation effect.3?10-5 mol/L N?-nitro-L-arginine-methyl-ester(L-NAME) and 10-5 mol/L indomethacin(Indo) could partly inhibit the relaxation effect of ACh to the rat basilar arteries,but non-No/non-PGI2-mediated relaxation was still significant(P

Electrolysis of physiological salt solution generates a factor that relaxes vascular smooth muscle

Oxygen-derived free radicals have been implicated in many important functions in the biological system. Electrical field stimulation (EFS) causes arterial relaxation in animal models. We found that EFS applied to neither muscle nor nerve but to Krebs solution caused a relaxation of rat aorta that had been contracted with phenylephrine. In the present study, therefore, we investigated the characteristics of this EIRF (electrolysis-induced relaxing factor) using rat isolated aorta. Results indicated that EIRF acts irrespective of the presence of endothelium. EIRF shows positive Griess reaction and is diffusible and quite stable. EIRF-induced relaxation was stronger on PE-contracted aorta than on KCl-contracted one, and inhibited by the pretreatment with methylene blue. Zaprinast, a cGMP-specific phosphodiesterase inhibitor, potentiated the EIRF-induced relaxation. NG-nitro-L-arginine, NO synthase inhibitor, did not inhibit the EIRF-induced relaxation. Deferroxamine, but not ascorbic acid, DMSO potentiated the EIRF-induced relaxation. These results indicate that electrolysis of Krebs solution produces a factor that relaxes vascular smooth muscle via cGMP-mediated mechanism.